肝癌介入诊疗理论与临床应用研究

本项目属临床医学研究。自1986年以来,通过对中晚期肝癌6000例次诊断性血管造影和介入性肝动脉插管化疗栓塞术,进行了系列性临床应用研究,其主要研究内容包括:(1)经单纯化疗、化疗碘油栓塞和化疗碘油明胶海绵栓塞三种方法的对照研究,以后者疗效最好,1年和3年生存率分别达到62.98％和13.92％。     

肝动脉灌注化疗和栓塞治疗老年肝脏恶性肿瘤

目的 观察用导管法肝动脉灌注化疗和栓塞治疗36例老年肝癌临床疗效。方法 将化疗药物经导管灌注肝动脉，化疗药与碘油混悬乳化流入肝肿瘤血管，再用明胶海绵颗粒栓塞血管。结果 经长期随访，存活≥5年l例，≥3年2例，≥2年2例，≥1年10例，9月以上2l例。结论 化疗栓塞后，病人症状缓解，甲胎蛋白值下降，肿瘤缩小，延长患者寿命。     

贲门癌的综合介入治疗疗效观察

目的观察经动脉化疗栓塞并内支架置放治疗中晚期贲门癌的临床效果。方法42例中晚期贲门癌患者除3例为临床诊断外其余均经内镜及病理学检查确诊。所有病例以Seldinger技术经股动脉穿刺插管，于肿瘤动脉内灌注化疗药物及栓塞剂并配合使用食管内支架置放术。灌注及栓塞以胃左动脉为主，少数辅以腹腔动脉、肝左动脉及左膈下动脉，所用栓塞剂为超液化碘油和明胶海绵颗粒。结果共行动脉灌注治疗143例次，平均3．4次/例，其中48例次加用碘油及明胶海绵颗粒栓塞。置放内支架47个。总有效率为88．1％(37／42)，半年、1年及2年生存率分别为82．0％(35／42)、69．1％(29／42)及38．0％(16／42)。结论经动脉灌注化疗栓塞并内支架置放的综合介入疗法是中晚期贲门癌安全有效的治疗措施。     

介入治疗原发性肝癌96例

目的观察介入治疗原发性肝癌的临床效果．方法肝癌患者96例，男66例，女30例，年龄28岁～70岁，平均年龄48．2岁．肝癌体积占肝脏55％以下，门脉无癌肿侵犯者．应用同轴导管系统，超导选择技术，介入治疗，药物选择：丝裂霉素20mg，表阿霉素50mg，5－FU500mg，配成40％的碘油冲注后，再进行栓塞术，对发现AFP回升肿瘤增大，栓塞动脉再通者再进行化疗栓塞，治疗问隔2mo～6mo不等，通过临床表现，影像学资料、生升指标进行临床评价．结果96例患者中，30例经一次治疗后病情稳定，20例患者进行第二次化疗栓塞，10例进行三次化疗栓塞，临床症状改善占70％，病灶缩小车55％，甲胎球下降率65％，术中1例瘤体破裂死亡，发热反应占30％，恶心、呕吐占35％，肝功能异常者占20％，1a存活率占70％，2a占15％，5a存活率1．2％．结论介入治疗原发性肝癌对不能手术切除患者提供了一种新的治疗手段，提高了肝癌患者的生存率．     

碘油化疗药物栓塞治疗肝细胞癌24例报告

目的分析碘油化疗药物栓塞治疗失去手术时机肝细胞癌的疗效。方法采用seldinger插管方法，将导管插入肝动脉或更接近肿瘤的供血动脉，先灌注化疗药物，再用碘油与化疗药物混悬液在X线监控下栓塞肿瘤血管，直至肿瘤区碘油沉积充分后再用明胶海绵栓塞。结果6个月生存率91．6％，12个月生存率41．6％，24个月生存率4．2％，平均生存13．6月。结论碘油化疗药物栓塞治疗中晚期肝细胞癌患者能适当延长病人的生存期。     

肝动脉灌注和栓塞治疗肝癌的护理体会

我院经肝动脉灌注和栓塞治疗原发性肝癌14例,其中男性13例、女性1例,年龄27～70岁。采用单纯导管化疗灌注4例,碘油乳剂加明胶海绵栓塞10例。现将护理体会总结如下。     

高温碘油热栓塞治疗原发性肝癌患者

目的 探讨高温碘油血管栓塞及热杀伤作用对原发性肝癌的疗效。方法 将131例原发性癌患者随机分为两组：热碘油栓塞组63例，化疗栓塞组68例。采用Seldinger方法，将导管超选择插入肿瘤供血动脉：（1）用110℃稀释热碘油脉冲式热栓塞；（2）用碘油化疗药物乳剂栓塞。结果 热栓塞组肿瘤小率和甲胎蛋白（AFP）复常率高于化疗栓塞组，而且术后临床不良反应轻，肝功能损害不明显，生存期较长。结论 高温稀释碘油流动性增加，对肿瘤滋养血管栓塞更为彻底，比热提高，对肿瘤细胞热杀伤作用增强。治疗原发性肝癌疗效好，不良反应轻，适应证广。     

经动脉热化疗治疗肝癌的临床应用

目的　研究经肝动脉灌注热化疗药治疗肝癌的有效性及安全性。方法　对３５ 例肝癌患者行肝动脉插管热化疗,碘油、５Ｆｕ 及卡铂加热至６０ ～６５°Ｃ后经导管灌入肝动脉,其余药物不加热。９例重复治疗,与同期１４ 例作２ 次或以上普通介入治疗的肝癌患者比较。４ 例热化疗后２ ～３ 个月手术切除,与同期普通介入治疗后手术切除的４ 例作比较。结果　热化疗组的肿瘤生长率为－ １０ ．０％±３３．３ ％ ,对照组的肿瘤生长率为３６ ．４％ ±５９．０％ ,差异有显著性（Ｐ＜ ０．０５） 。手术切除标本的坏死率（大体）分别为９３．５ ％ ±５ ．９７ ％ 及７３．５ ％ ±２８ ．３８ ％ ,但差异无显著性,显微镜下观表现相似。肝动脉损伤各一例。热化疗组中１９ 例行“夹心面包”疗法,与普通“夹心面包”疗法的２２ 例比较,其轻、中度毒副反应分别为７３．７％ 和６３．６％ ,重度反应为２６ ．３ ％ 和３７ ．４ ％ ,但差异无显著性。结论　经肝动脉灌注６０～６５°Ｃ的碘油、化疗药合并明胶海绵栓塞肝动脉治疗肝癌是简单、安全的方法,能显著提高单纯化疗、栓塞的疗效。     

经肝动脉免疫化疗栓塞术治疗晚期肝癌

目的 探讨经肝动脉免疫化疗栓塞对晚期肝癌的疗效及对机体免疫功能的影响。 方法 晚期肝癌12例,经肝动脉灌注细胞因子-化疗药物-碘油乳剂,即由rIL-2 40-60万U,rIFN 160万U,TNF100万U,ADM 20 mg,MMC 10 mg和碘油8-15 ml混合乳化制成的乳剂。共两次,间隔2周。第2次灌注术后用明胶海绵行肝动脉栓塞。 结果 治疗后1个月,7例瘤体缩小,2例稳定,3例增大。10例AFP阳性者5例明显下降。术后外周血NK活性显著增强。 结论 经肝动脉免疫化疗栓塞术对晚期肝癌疗效较满意,副作用小,并能明显改善机体免疫功能,值得进一步探讨。     

经导管栓塞化疗中晚期肝癌

目的研究中晚期肝癌非手术治疗的最佳方案。方法135例随机分成Ａ、Ｂ、Ｃ３组。Ａ组肝动脉内灌注化疗药物，Ｂ组药物灌注加碘油乳剂及明胶海绵栓塞，Ｃ组碘油乳剂及明胶海绵栓塞。结果３组平均生存期为5.7月，10.6月和8.7月；0.5、１、２、３年生存率Ａ组51.6％、12.9％，无     

Clinical evaluation of transcatheter arterial embolization and one-shot chemotherapy in hepatocellular carcinoma

The therapeutic effect and the prognosis of transcatheter arterial embolization (TAE) and one-shot chemotherapy were studied in 90 cases of unresectable hepatocellular carcinoma (HCC). A therapeutic effect, which was assessed by the serum concentration of alpha-fetoprotein, angiography, computed tomography and ultrasonography, was seen in 33 (83%) out of 40 cases treated with TAE, and in 16 (32%) out of 50 cases treated with one-shot chemotherapy. In the cases that received TAE, the cumulative percentage survival rates at 6 months, 12 months, and 24 months were 75%, 48% and 20%, respectively. In contrast, the survival rates in the cases that received one-shot chemotherapy were 30%, 10% and 2%, respectively. In addition, the prognosis on the basis of the degree of tumor invasion of the portal vein was studied. In cases with the same degree of tumor invasion, the survival rate of the cases treated with TAE was significantly higher than that of those treated with one-shot chemo-therapy, except for those cases with tumor invasion of the main portal vein. These results show that TAE should be performed as the therapy of first choice in unresectable cases of HCC.     

Quantitative analysis of plasma HBV DNA for early evaluation of the response to transcatheter arterial embolization for HBV-related hepatocellular carcinoma

AIM: To assesse changes in plasma HBV DNA after TAE in HBV-related HCC and correlate the levels with the pattern of lipiodol accumulation on CT. METHODS: Between April and June 2001,14 patients with HBV-associated HCC who underwent TAE for inoperable or recurrent tumor were studied. Levels of plasma HBV DNA were measured by real-time quantitative PCR daily for five consecutive days after TAE. More than twofold elevation of circulating HBV DNA was considered as a definite elevation. Abdominal CT was performed 1-2 mo after TAE for the measurement of lipiodol retention. RESULTS: Circulating HBV DNA in 10 out of 13 patients was elevated after TAE, except for one patient whose plasma HBV DNA was undetectable before and after TAE. In group Ⅰ patients (n = 6), the HBV DNA elevation persisted for more than 2 d, while in group Ⅱ (n = 7), the HBV DNA elevation only appeared for 1 d or did not reach a definite elevation. There were no significant differences in age or tumor size between the two groups. Patients in group Ⅰ had significantly better lipiodol retention (79.31±28.79%) on subsequent abdominal CT than group Ⅱ (18.43±10.61%) (P=0.02). CONCLUSION: Patients with durable HBV DNA elevation for more than 2 d correlated with good lipiodol retention measured 1 mo later, while others associated with poor lipiodol retention. Thus, circulating HBV DNA may be an early indicator of the success or failure of TAE.     

Acute pancreatitis after transcatheter arterial embolization (TAE) for hepatocellular carcinoma

Transcatheter arterial embolization (TAE) has been widely used for treatment of hepatocellular carcinoma. Acute pancreatitis occasionally occurs as a complication of TAE. We have investigated the possible effects of TAE on the pancreas by monitoring serum pancreatic enzyme activities following TAE with various embolic materials. Serum amylase activity was increased very little in the patients treated with chemotherapy alone or plus TAE with lipiodol, slightly increased in many of the patients treated with chemotherapy plus TAE with gelatin sponge, and increased in all of the patients treated with chemotherapy plus TAE with gelfoam powder. The activity was increased to a level as high as 700 U/dl or more in most individuals of the last category. In one of them acute pancreatitis developed, probably because the gelfoam powder regurgitated into the pancreaticoduodenal artery, and occluded a very peripheral portion of the pancreatic vascular bed, leading to ischemia of the pancreas. These results suggest that choosing the correct particle size is important for prevention of acute pancreatitis.     

Transarterial embolization ablation of hepatocellular carcinoma with a lipiodol-ethanol mixture

AIM: To determine the safety and effectiveness of transarterial embolization ablation (TEA) of hepatocellular carcinoma (HCC) with a lipiodol-ethanol mixture. METHODS: Between January 1 and December 31, 2009, 15 patients with HCC (13 men/two women, aged 38-75 years) accepted TEA treatment and were enrolled in this study, including five newly diagnosed patients and 10 with refractory disease. Two months after TEA, angiography and contrast computed tomography (CT) were performed, and responses were assessed using a modified version of Response Evaluation Criteria in Solid Tumors (RECIST version 1.1). The follow-up period was to June 30, 2010. RESULTS: Every new case was treated once. Angiography was performed immediately after TEA, and showed that the tumor-feeding vessels were completely embolized and that lipiodol was densely deposited inside tumors. Two months after treatment, contrast CT showed no enhanced lesions. Alpha fetoprotein levels returned to normal in four patients and markedly decreased in another. mean ± SD survival after treatment was 10.8 ± 4.5 mo. All five patients survived during the follow-up period. Ten patients with refractory disease were treated a total of 14 times. Angiography immediately after TEA showed that blood flow to the tumors was obviously decreased in all cases, and contrast CT showed obvious depositions of lipiodol. Two months after treatment, the tumors had shrunk (6/10) or were stable (3/10). One had progressed after 2 mo and died of tumor rupture 3 mo after TEA. mean ± SD survival after treatment was 8.6 ± 4.3 mo; two patients survived during the follow-up period. Adverse effects included reversible hepatic decompensation, upper abdominal pain, and fever. CONCLUSION: TEA is an effective therapy for patients with HCC and might be more effective than transcather arterial chemoembolization for treating refractory disease.     

Diagnosis, treatment and prognosis of small hepatocellular carcinoma

Diagnosis, treatment and prognosis of hepatocellular carcinoma (HCC) of small size, not larger than 5 cm in diameter, were studied in forty-three patients with underlying cirrhosis, who were detected among one-hundred-and-sixty-five HCC cases over a period of 4.5 years from 1981 to 1985. The patients included fifteen cases with tumors smaller than 3 cm in diameter which were diagnosed HCC mostly during the follow-up period of liver cirrhosis. Among various imaging procedures, real-time linear scan ultrasonography (US) had a 91% positive HCC detection rate, hepatic angiography 93% and computed tomography (CT) 88%. Surgical treatment including partial resection, subsegmentectomy and segmentectomy, was carried out in fifteen HCC cases with well-compensated cirrhosis. Transcatheter arterial embolization (TAE) was performed in nineteen cases with severe liver dysfunction and multiple location of tumors. Three-year survival was 80% in twelve patients with hepatic resection (performed since 1981) and 19% in the TAE cases; none of the other cases survived.     

Evaluation of transcatheter arterial embolization prior to percutaneous tumor ablation in patients with hepatocellular carcinoma: a randomized controlled trial.

BACKGROUND: Transcatheter arterial embolization (TAE) may reduce the risk of hepatocellular carcinoma (HCC) recurrence when performed before percutaneous tumor ablation (PTA), either percutaneous ethanol injection therapy (PEIT) or radiofrequency ablation (RFA). We conducted a randomized, controlled trial comparing the use of TAE combined with percutaneous ethanol injection therapy (TAE/PEIT) to the use of PEIT only to assess the effects on HCC recurrence and survival. We continued the study after the introduction of RFA and compared TAE combined with RFA (TAE/RFA) with RFA only. METHODS: Between March 1997 and April 2001, 42 HCC patients were enrolled who satisfied the following inclusion criteria: (1) uninodular HCC as determined by angiography under computed tomography, (2) arterial hypervascularity, and (3) no prior history of HCC treatment. Twenty-two patients were treated with TAE/PTA (PEIT, 12; RFA, 10) and 20 patients with PTA only (PEIT, 14; RFA, 6). RESULTS: There were four cases of local recurrence in the PTA-only group and none in the TAE/PTA group (P=0.043). The four patients with local recurrence were treated with PEIT. None of the patients treated with RFA showed local recurrence. The effect of TAE on overall recurrence was not significant (P=0.4179). In the multivariate analysis, prior TAE was not significant for survival (P=0.514). CONCLUSIONS: TAE has a limited use in suppressing local recurrence when performed before PEIT but not before RFA.     

Use of fructose 1,6-diphosphate aldolase to detect tumour necrosis after transcatheter arterial embolization of hepatocellular carcinoma

Transcatheter arterial embolization (TAE) is a popular and well-established devascularization treatment modality for hepatocellular carcinoma (HCC). The persistent retention of lipiodol on follow-up computed tomography (CT) scan and time-dependent decrease in size of the lipiodol-stained area of tumour after TAE does not reveal the biological death of tumour cells. Moreover, it is difficult to clinically evaluate the effective necrosis of tumour cells by TAE in cases of HCC that do not produce alpha-fetoprotein (AFP). We therefore studied the release of a relatively tumour-specific protein by the necrotic hepatoma cells to evaluate the effectiveness of TAE. Transcatheter arterial embolization was performed in 17 patients with the imaging diagnosis of HCC; either superselective (n = 6) or non-superselective (n = 11) techniques were used. We measured serum levels of relatively tumour-specific fructose 1,6-diphosphate (FDP) aldolase and non-tumour-specific fructose 1-phosphate (F1P) aldolase by substrate-specific enzymatic methods. Enzyme activities were performed before and after TAE. The time-dependent decrease in size of the lipiodol-stained areas was studied on follow-up CT scans after TAE. Pre- and post-treatment serum AFP levels were determined by radio-immunoassay. The six cases of superselective TAE underwent marked tumour regression by CT compared with the 11 cases of non-superselective TAE. Fructase 1,6-diphosphate aldolase output correlated well with post-necrotic tumour regression after TAE (r = 0.87, P= 0.001). The elevation of serum FDP aldolase was also significantly associated with a decrease in serum AFP (r = 0.72, P < 0.01). In contrast, serum F1P aldolase output was inversely correlated with either tumour regression or serum AFP concentrations after TAE. The serum levels of the tumour-specific enzyme FDP aldolase correlated significantly with effective tumour necrosis and consequent tumour regression after TAE. We suggest that measurement of FDP aldolase activity in serum after TAE can be used clinically to detect the degree of tumour necrosis by TAE.     

Treatment for extrahepatic metastasis of hepatocellular carcinoma following successful hepatic resection

BACKGROUND/AIMS: Recent advances in both the diagnosis and treatment of hepatocellular carcinoma (HCC) have improved its prognosis. Intrahepatic recurrence after hepatectomy can be treated with repeated hepatectomy, transhepatic arterial embolization (TAE), percutaneous ethanol injection therapy (PEIT), or microwave coagulo-necrotic therapy. However, treatment for extrahepatic recurrence is also important in prolonging survival in some patients. METHODOLOGY: After radical hepatectomy in 155 patients, extrahepatic recurrences were found in 15 patients that underwent subsequent treatment. The interval between completing treatment for the primary tumor and the discovery of metastasis, the location and mode of treatment of the metastasis, and the outcomes were analyzed. RESULTS: Distant metastasis was detected at a mean of 7 months after radical resection of the primary tumor. Location of the metastasis included lung, bone, and adrenal gland. Four patients had no intrahepatic recurrence and 11 patients had simultaneous intrahepatic recurrence. Six patients with intrahepatic and extrahepatic recurrence that underwent systemic chemotherapy had poor prognoses, and all died within 12 months as a result of progression of the intrahepatic tumor. Five patients with intra- and extrahepatic recurrence that underwent systemic chemotherapy combined with hepatic arterial infusion chemotherapy had relatively good outcomes; all survived for more than 12 months. CONCLUSIONS: These results suggest that to obtain a good prognosis for extrahepatic metastasis coexisting with intrahepatic recurrence, intrahepatic recurrence should be controlled by locoregional therapy, and extrahepatic metastasis should be controlled by systemic chemotherapy and/or irradiation therapy.     

Therapeutic radiological interventional procedures in hepatocellular carcinoma.

BACKGROUND: To improve the survival rate of patients with hepatocellular carcinoma (HCC) in whom surgery is not possible, various methods have been developed employing angiographic and percutaneous techniques. We analyzed our experience with various percutaneous therapeutic interventional techniques done for HCC in our center. METHODS: Sixty-one patients with inoperable HCC (mean age 48.9 [SD 13.8] y; 47 men) were treated between January 1997 and December 2000 by transcatheter arterial chemoembolization (TACE) alone (22), TACE with percutaneous alcohol injection (PEI) (20), transcatheter arterial embolization (TAE) with steel coils and gel foam for gastrointestinal bleed (7), percutaneous radiofrequency ablation (1), percutaneous preoperative right portal vein embolization (3) and percutaneous preoperative tumor embolization to reduce blood loss at surgery (8). RESULTS: In 42 patients treated by TACE and PEI and TACE alone, tumor necrosis was scored; over 50% necrosis was seen only after six and nine months in both treatment groups. The survival rates after six and nine months and the median survival were similar in the two groups. Of 7 cases treated with TAE with steel coils and gel foam, the gastrointestinal bleeding stopped in four; in the other three, bleeding did not stop completely although less transfusion was required. In the patient treated by radiofrequency ablation, follow-up contrast-enhanced CT did not show enhancing tumor mass. We noted left lobe enlargement after percutaneous preoperative right portal vein embolization, prior to right hepatectomy. CONCLUSION: In patients with HCC not amenable to surgical intervention, a variety of percutaneous therapeutic interventional techniques may be used.     

Imaging diagnosis of ruptured site in hepatocellular carcinoma

Rupture causes frequently the patients with HCC to death. Then it is important to investigate ruptured site of HCC in order to stop bleeding effectively and safely by emergent TAE without causing liver failure. We evaluate the usefulness of 3 major imaging method, such as US, CT and angiography in our 18 cases of HCC. In ultrasonography, ruptured site was shown as the high echoic area localized around the tumor in 4/15 cases (26.7%). In computed tomography of rapid scanning, it was shown as the intraperitoneal high density area around the tumor in 3/18 cases (16.7%). And lipiodol CT showed the characteristic leakage in the abdominal cavity. In angiography, it was shown as the extravasation of contrast material only in 2/13 cases (15.4%). In the results, it was possible to diagnose the ruptured site in 8/18 cases (44.4%) by using these procedures. Diagnosis of ruptured site will make it possible to reduce the frequency of hepatic failure caused by emergent TAE.